Although many leading researchers have come up with various definitions of what tissue engineering is, the ultimate goal of the tissue engineering is all the same in that it is a technology which combines bioscience knowledge with engineering knowledge to regenerate damaged organs.
Although many factors should be taken into account for successful tissue regeneration, various approaches have been attempted, depending on physical, biological, and chemical characteristics of desired tissues, focusing on mainly three crucial components.
The first component is cells that constitute the vast majority of tissues. Essentially, the human organs, such as skin, blood vessels, nerves, bones, and mussels, are composed of cells, and because the organs that are subjects of tissue engineering are different in the kind, composition, and function of their constituent cells, it is necessary to fully consider how each cell can be used. Regeneration of function, rather than simply regeneration of form, is the most important goal, and thus cells that are best suited to the tissue to be regenerated should be used.
The second crucial component of the tissue engineering is a biomaterial. As mentioned above, tissue is a system in which a variety of cells are fused to form organisms. Thus, there is an ideal tissue form or cell composition for regenerating specific tissue and a biomaterial acts as a framework for developing organism of fused cells.
In addition, for ideal tissue regeneration, the biomaterial needs to meet various essential properties. The representative properties include (1) biodegradability and non-toxic, (2) interconnected internal porous structure with a large surface area, (3) structural stability, (4) provision of a cellular adsorption, (5) low immunoreactivity, (6) inhibition of thrombus formation, (7) hydrophilicity, and (8) biofunctionality.
Finally, in order to artificially grow tissues, it is necessary to implement a human-like cellular environment that can regulate the physiological activities of cells on the basis of cells and biomaterial.
In a new tissue engineering approach that does not provide cells, the role of bioactive molecules is crucial. The bioactive molecules are an important factor that can control the environment of our body, and they are composed of growth factors or cytokine. The bioactive molecules regulate the migration, proliferation, differentiation and homing of stem cells or progenitor cells present in the body, thereby securing enough stem cell counts in the transplanted biomaterial to induce effective tissue regeneration.
In order to deliver effective bioactive molecules for regeneration of tissues, it is necessary to spatially and temporally controlled release of bioactive molecules with sufficient bioactivity for a long period of time.
However, most of the bioactive molecules are easily degraded by enzymes present in the body or are liable to lose activity, and a bolus injection at a target site may cause cytotoxicity due to a high concentration of bioactive molecules at the time of injection.
For these reasons, the bioactive molecules are locally transferred using a sustained-release delivery method that chemically immobilizes or incorporates the bioactive molecules into a biomaterial and releases the biomaterial slowly while maintaining a specific effective concentration. This delivery method is dependent on the properties of the material, which controls and the release of bioactive molecules according to temperature, pH, electromagnetic field, degree of biodegradation of polymer, and the like.
Conventional methods for sustained release of bioactive molecules include covalent immobilization using surface modification and heparin intermediated immobilization using heparin as an additive.
The covalent immobilization through surface modification is a method of immobilizing growth factors by modifying a surface of the biomaterial with an amine group, hydrolyzing growth factors by use of 1-ethyl-3-(3-dimethylaminopropyl)-1-carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) to expose carboxyl groups to the surface, thereby fixing the amine group of the surface of the biomaterial and the carboxyl groups of the growth factors with covalent bonds.
In addition, the heparin intermediated immobilization is a method which is widely used to effectively introduce growth factors into a porous biomaterial, wherein heparin acts as an intermediator which links a polymer surface with the growth factors. Generally, heparin can be introduced from the polymer surface via covalent bonds with amine groups present on the polymer surface, or through hydrogen bonding with O-functional groups existing on the polymer surface, and then, the growth factors may be immobilized on the surface of the biomaterial through ionic bonds between O-sulfate/N-sulfate existing in the heparin and lysine/arginine of the growth factors (See Patent Document 1).
However, it is known that the covalent bonds between the amine groups existing on the surface of the biomaterial and heparin degrades the biological function of heparin, thereby lowering the interaction with the growth factors. In addition, the above two methods are too complicated and have a disadvantage that EDC/NHS exhibits a harmful toxicity to a human body.
Therefore, a biomaterial for tissue regeneration which maintains a bioactivity for a long period of time without using toxic additives for sustained release of bioactive molecules and is harmless to a human body has not yet been developed.